反应详情

温度

60 °C

tert-Butyl (2R,5R)-2-[2-(3-{[N-(tert-butoxycarbonyl)-4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]amino}-5-fluoropyridin-4-yl)ethyl]-5-(hydroxymethyl)morpholine-4-carboxylate (1.50 g, 2.10 mmol) and CDI (0.425 g, 2.62 mmol) were heated at 60° C. in Pyridine (21 mL) for 30 min. 2,2,2-Trifluoroethylamine (3.29 mL, 42.0 mmol) was added and the reaction heated at 60° C. for 24 hours, A further aliquot of 2,2,2-Trifluoroethylamine (1.65 mL, 21.0 mmol) was added and the reaction heated at 60° C. for a further 24 hours. The reaction was quenched with saturated aqueous KH2PO4 then brine and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. Purification on silica gel (220 g) eluting with a gradient of 0-100% EtOAc/hexanes afforded the title compound (1.29 g, 1.54 mmol, 73% yield) as a white solid, MS (ESI): m/z=840.46 (MH+); 100% pure by LCMS.

1. temperaturethe reaction heated at 60° C. for a further 24 hours
2. customThe reaction was quenched with saturated aqueous KH2PO4
3. extractionbrine and the mixture was extracted with ethyl acetate (×3)
4. dry with materialThe combined organic fractions were dried (MgSO4)
5. filtrationfiltered
6. customthe solvent was evaporated under reduced pressure
7. customPurification on silica gel (220 g)
8. washeluting with a gradient of 0-100% EtOAc/hexanes